Crystal structure of mutant LOX-1, a receptor protein for oxidized LDL

Introduction LOX-1, the lectin-like oxidized low-density lipoprotein (LDL) receptor, is the major receptor for oxidized LDL (OxLDL). This enzyme plays a critical role in endothelial dysfunction and injury, leading to initiation and progression of atherosclerosis. LOX-1 belongs to the Ctype lectin family, and human LOX-1 constitutes of cytoplasmic domain, transmembrane domain (TM), NECK domain and c-type lectin domain (CTLD), as the order from N-terminal. Crystal structure of LOX-1 ligand binding domain (CTLD-NECK14; C-termini 14 residues of NECK domain and whole CTLD domain, residue range 143-270) was already determined at 1.8 Å resolution by one of the author (ST)’s group [1]. LOX-1 forms homo dimer in physiological condition, and two Trp150s of each molecule are facing to each other, and this residue is expected to play an important role for the dimer formation In fact, it was found that the mutant W150A loses the ability of dimerization. This dimerization mechanism was approached by using surface plasmon resonance [2], and its dynamics are now progressing by NMR spectroscopy. In this study, in order to elucidate the detailed molecular mechanism, the crystal structure of W150A mutant of CTLD-NECK14 domain was studied.